Immunogenicity and protective efficacy of orally administered recombinant Lactococcus lactis expressing surface-bound HIV Env

Abstract This study investigates whether genetically modified orally administered Lactococcus lactis (L lactis) could be used as an HIV vaccine. L lactis is immunogenic and extremely safe when delivered orally. We created a recombinant L lactis vector expressing the envelope protein of HIV on its cell surface. Oral immunization with this vector induced high levels of HIV-specific serum IgG and fecal IgA antibodies. Cell-mediated immune responses also were generated in both the regional lymph nodes and the spleen. Dendritic cells are readily infected by L lactis and appear to play a potential role in mediating the development of these immune responses. The protective efficacy of this vaccine strategy was demonstrated by challenging mice intraperitoneally with an HIV Env–expressing vaccinia virus. Their viral loads were 350-fold lower than those of control mice. These findings support the further development of L lactis–based HIV vaccines. (Blood. 2003; 102:223-228)

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Oral immunization with a recombinant Lactococcus lactis expressing HIV-1 Gag on the tip of the pilus induces strong mucosal immune responses

Retrovirology ◽

10.1186/1742-4690-9-s2-o12 ◽

2012 ◽

Vol 9 (S2) ◽

Author(s):

V Chamcha ◽

JR Scott ◽

R Amara

Keyword(s):

Immune Responses ◽

Lactococcus Lactis ◽

Oral Immunization ◽

Mucosal Immune Responses ◽

Recombinant Lactococcus Lactis ◽

Hiv 1

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Immune responses elicited in mice with recombinant Lactococcus lactis expressing F4 fimbrial adhesin FaeG by oral immunization

Veterinary Research Communications ◽

10.1007/s11259-010-9418-x ◽

2010 ◽

Vol 34 (6) ◽

pp. 491-502 ◽

Cited By ~ 9

Author(s):

Shujie Liu ◽

Yongming Li ◽

Ziwei Xu ◽

Yicheng Wang

Keyword(s):

Immune Responses ◽

Lactococcus Lactis ◽

Oral Immunization ◽

Recombinant Lactococcus Lactis ◽

Fimbrial Adhesin

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Oral immunization of a non-recombinant Lactococcus lactis surface displaying influenza hemagglutinin 1 (HA1) induces mucosal immunity in mice

PLoS ONE ◽

10.1371/journal.pone.0187718 ◽

2017 ◽

Vol 12 (11) ◽

pp. e0187718 ◽

Cited By ~ 4

Author(s):

Pui-Fong Jee ◽

Vunjia Tiong ◽

Meng-Hooi Shu ◽

Jing-Jing Khoo ◽

Won Fen Wong ◽

...

Keyword(s):

Lactococcus Lactis ◽

Mucosal Immunity ◽

Oral Immunization ◽

Influenza Hemagglutinin ◽

Recombinant Lactococcus Lactis

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Oral immunization with recombinant hepatitis E virus antigen displayed on the Lactococcus lactis surface enhances ORF2-specific mucosal and systemic immune responses in mice

International Immunopharmacology ◽

10.1016/j.intimp.2014.10.032 ◽

2015 ◽

Vol 24 (1) ◽

pp. 140-145 ◽

Cited By ~ 19

Author(s):

Shenyang Gao ◽

Dandan Li ◽

Ying Liu ◽

Enhui Zha ◽

Tiezhong Zhou ◽

...

Keyword(s):

Immune Responses ◽

Lactococcus Lactis ◽

Hepatitis E Virus ◽

Hepatitis E ◽

Oral Immunization ◽

Virus Antigen ◽

Recombinant Hepatitis

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Oral vaccine of recombinant Lactococcus lactis expressing the VP1 protein of duck hepatitis A virus type 3 induces mucosal and systemic immune responses

Vaccine ◽

10.1016/j.vaccine.2019.06.026 ◽

2019 ◽

Vol 37 (31) ◽

pp. 4364-4369 ◽

Cited By ~ 4

Author(s):

Shasha Song ◽

Pengfei Li ◽

Ruihua Zhang ◽

Junhao Chen ◽

Jingjing Lan ◽

...

Keyword(s):

Immune Responses ◽

Lactococcus Lactis ◽

Virus Type ◽

Hepatitis A ◽

Hepatitis A Virus ◽

Oral Vaccine ◽

Vp1 Protein ◽

Duck Hepatitis ◽

Recombinant Lactococcus Lactis ◽

Type 3

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Expression of two Listeria monocytogenes antigens (P60 and LLO) in Lactococcus lactis and examination for use as live vaccine vectors

Journal of Medical Microbiology ◽

10.1099/jmm.0.018770-0 ◽

2010 ◽

Vol 59 (8) ◽

pp. 904-912 ◽

Cited By ~ 20

Author(s):

Mohammed Bahey-El-Din ◽

Pat G. Casey ◽

Brendan T. Griffin ◽

Cormac G. M. Gahan

Keyword(s):

Immune Response ◽

Listeria Monocytogenes ◽

Lactococcus Lactis ◽

Protective Efficacy ◽

Oral Immunization ◽

Listeriolysin O ◽

Oral Vaccination ◽

Vaccine Vectors ◽

Food Borne ◽

Presentation Pathway

Listeria monocytogenes is a food-borne intracellular pathogen that mainly infects pregnant and immunocompromised individuals. The pore-forming haemolysin listeriolysin O (LLO), the main virulence factor of Listeria monocytogenes, allows bacteria to escape from the harsh environment of the phagosome to the cytoplasm of the infected cell. This leads to processing of bacterial antigens predominantly through the cytosolic MHC class I presentation pathway. We previously engineered the food-grade bacterium Lactococcus lactis to express LLO and demonstrated an LLO-specific CD8+ response upon immunization of mice with the engineered L. lactis vaccine strains. In the present work, we examined the immune response and protective efficacy of an L. lactis strain co-expressing LLO and a truncated form of the listerial P60 antigen (tP60). Oral immunization revealed no significant protection against listeriosis with L. lactis expressing LLO, tP60 or the combined LLO/tP60. In contrast, intraperitoneal vaccination induced an LLO-specific CD8+ immune response with LLO-expressing L. lactis but no significant improvement in protection was observed following vaccination with the combined LLO/tP60 expressing L. lactis strain. This may be due to the low level of tP60 expression in the LLO/tP60 strain. These results demonstrate the necessity for improved oral vaccination strategies using LLO-expressing L. lactis vaccine vectors.

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Oral immunization with Lactococcus lactis-expressing EspB induces protective immune responses against Escherichia coli O157:H7 in a murine model of colonization

Vaccine ◽

10.1016/j.vaccine.2014.05.054 ◽

2014 ◽

Vol 32 (31) ◽

pp. 3909-3916 ◽

Cited By ~ 29

Author(s):

B. Ahmed ◽

M. Loos ◽

D. Vanrompay ◽

E. Cox

Keyword(s):

Escherichia Coli ◽

Immune Responses ◽

Lactococcus Lactis ◽

Murine Model ◽

Oral Immunization ◽

Escherichia Coli O157

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Oral Immunization with Recombinant Vaccinia Virus Prime and Intramuscular Protein Boost Provides Protection against Intrarectal Simian-Human Immunodeficiency Virus Challenge in Macaques

Clinical and Vaccine Immunology ◽

10.1128/cvi.00597-15 ◽

2015 ◽

Vol 23 (3) ◽

pp. 204-212 ◽

Cited By ~ 7

Author(s):

Rajesh Thippeshappa ◽

Baoping Tian ◽

Brad Cleveland ◽

Wenjin Guo ◽

Patricia Polacino ◽

...

Keyword(s):

Human Immunodeficiency Virus ◽

Immune Responses ◽

Vaccinia Virus ◽

Protective Efficacy ◽

Recombinant Vaccinia Virus ◽

Oral Immunization ◽

Recombinant Vaccinia ◽

Immunodeficiency Virus ◽

Vaccinia Viruses ◽

Hiv 1

ABSTRACTHuman immunodeficiency virus type 1 (HIV-1) acquisition occurs predominantly through mucosal transmission. We hypothesized that greater mucosal immune responses and protective efficacy against mucosal HIV-1 infection may be achieved by prime-boost immunization at mucosal sites. We used a macaque model to determine the safety, immunogenicity, and protective efficacy of orally delivered, replication-competent but attenuated recombinant vaccinia viruses expressing full-length HIV-1 SF162 envelope (Env) or simian immunodeficiency virus (SIV) Gag-Pol proteins. We examined the dose and route that are suitable for oral immunization with recombinant vaccinia viruses. We showed that sublingual inoculation of two vaccinia virus-naive pigtailed macaques with 5 × 108PFU of recombinant vaccinia viruses was safe. However, sublingual inoculation with a higher dose or tonsillar inoculation resulted in secondary oral lesions, indicating the need to optimize the dose and route for oral immunization with replication-competent vaccinia virus vectors. Oral priming alone elicited antibody responses to vaccinia virus and to the SF162 Env protein. Intramuscular immunization with the SF162 gp120 protein at either 20 or 21 weeks postpriming resulted in a significant boost in antibody responses in both systemic and mucosal compartments. Furthermore, we showed that immune responses induced by recombinant vaccinia virus priming and intramuscular protein boosting provided protection against intrarectal challenge with the simian-human immunodeficiency virus SHIV-SF162-P4.

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